Urea substituted imidazoquinolines

Abstract

Imidazoquinoline and tetrahydroimidazoquinoline compounds that contain urea, thiourea, acylurea, or sulfonylurea functionality at the 1-position are useful as immune response modifiers. The compounds and compositions of the invention can induce the biosynthesis of various cytokines and are useful in the treatment of a variety of conditions including viral diseases and neoplastic diseases.

1. A compound of the formula (I): 
                 
 
       wherein
 bonds represented by the dashed lines are present;  
 R 1  is —C 1-10  alkyl-NR 3 —CY—NR 5 —R 4    
 Y is O;  
 R 4  is C 1-10  alkyl;  
 R 2  is selected from the group consisting of C 1-4  alkyl and C 1-4  alkyl-O—C 1-4  alkyl;  
 R 3  is hydrogen;  
 R 5  is hydrogen, or R 4  and R 5  combine to form a morpholine ring;  
 each R present is independently selected from the group consisting of C 1-10  alkyl, C 1-10  alkoxy, halogen, and trifluoromethyl; and  
 n is 0;  
 
       or a pharmaceutically acceptable salt thereof. 
     
     
       2. The compound or salt of  claim 1  wherein R 4  is ethyl, 1-methylethyl, or n-propyl; and R 2  is C 1-4  alkyl, ethoxymethyl, or methoxyethyl. 
     
     
       3. The compound or salt of  claim 1  wherein R 4  and R 5  combine to form a morpholine ring. 
     
     
       4. A pharmaceutical composition comprising a therapeutically effective amount of a compound or salt of  claim 1  in combination with a pharmaceutically acceptable carrier. 
     
     
       5. A pharmaceutical composition comprising a therapeutically effective amount of a compound or salt of  claim 2  in combination with a pharmaceutically acceptable carrier. 
     
     
       6. A pharmaceutical composition comprising a therapeutically effective amount of a compound or salt of  claim 3  in combination with a pharmaceutically acceptable carrier. 
     
     
       7. A method of inducing cytokine biosynthesis in an animal comprising administering a therapeutically effective amount of a compound or salt of  claim 1  to the animal. 
     
     
       8. A method of inducing cytokine biosynthesis in an animal comprising administering a therapeutically effective amount of a compound or salt of  claim 2  to the animal. 
     
     
       9. A method of inducing cytokine biosynthesis in an animal comprising administering a therapeutically effective amount of a compound or salt of  claim 3  to the animal. 
     
     
       10. A method of treating a viral disease in an animal comprising administering a therapeutically effective amount of a compound or salt of  claim 1  to the animal. 
     
     
       11. A method of treating a viral disease in an animal comprising administering a therapeutically effective amount of a compound or salt of  claim 2  to the animal. 
     
     
       12. A method of treating a viral disease in an animal comprising administering a therapeutically effective amount of a compound or salt of  claim 3  to the animal. 
     
     
       13. A method of treating a neoplastic disease in an animal comprising administering a therapeutically effective amount of a compound or salt of  claim 1  to the animal. 
     
     
       14. A method of treating a neoplastic disease in an animal comprising administering a therapeutically effective amount of a compound or salt of  claim 2  to the animal. 
     
     
       15. A method of treating a neoplastic disease in an animal comprising administering a therapeutcially effective amount of a compound or salt of  claim 3  to the animal.